What's New 2003

Two fundraising events were held in different areas of the country to benefit pancreatic cancer research at John Hopkins. These fundraisers honored two very special men, helped to raise critical money to fight this dreadful disease, and celebrated November as Pancreas Cancer Awareness Month.

"The Second Annual Ride to Make a Difference for Pancreatic Cancer" was held in Atlanta, Georgia by the Joseph C. Monastra Foundation for Pancreatic Cancer Research. Held on a beautiful day with a full police escort of 5 motorcycle cops, the 75-mile ride was safe, smooth and enjoyable. The generosity shown by the biker community of Georgia was overwhelming with one auction item being donated back after being sold only to be sold again. To learn more about this remarkable family and their fundraising efforts, visit our Web site's overview of the Monastra family and Foundation.

The George Rubis Endowment for Pancreatic Cancer Research held "The First Annual Run for George" in Englewood Cliffs, New Jersey. The 5K race, silent auction, food and carnival games were enjoyed by the family, friends, and the local community in honor of George Rubis' memory and to support pancreatic cancer research at Johns Hopkins. Kieran Brune, Coordinator of the National Familial Pancreas Tumor Registry, ran the 5K event and spoke to those in attendance.

New Pathway for Cancer Discovered in HedgehogSeptember 17, 2003

Friends — I wanted to update you on a remarkable discovery from the pancreatic cancer research team here at Johns Hopkins. Today the journal Nature released an on-line version of a paper by Drs. Berman, Maitra and Beachy in which they demonstrate the activation of the "sonic hedgehog gene" in pancreatic and biliary cancers (http://www.nature.com/nature). The complete print version will appear in a few weeks in Nature.

"Sonic hedgehog" is part of a cell pathway that plays an important role in embryogenesis. Cell pathways are groups of proteins within cells that interact/communicate with each other. Embryogenesis is the formation of the embryo. Dr. Beachy discovered several of the key components of this pathway, studying, of all things, fruit fly genetics. It was shown that alterations in the sonic hedgehog pathway caused fruit fly larva to look like, you guessed it, the computer game character "sonic hedgehog". Dr. Beachy's team then went on to show that this same pathway is important in human embryogenesis and that the sonic hedgehog pathway plays a key role in maintaining stem cells in our bodies. Dr. Beachy was elected to the National Academy of Science for this work. Now, Drs. Beachy, Maitra and Berman team together to show that the sonic hedgehog pathway is activated in human cancers, including cancers of the pancreas and biliary tree. Furthermore, they show that when they block the pathway using a drug called cyclopamine, that they completely block tumor growth.

This paper is very exciting to me for several reasons. First, it helps us understand the fundamental biology of pancreatic and biliary cancer. Their data show that a pathway that regulates stem cells is altered in these cancers (for scientists this is a very exciting idea). Second, the discovery of this pathway's role in human pancreatic and biliary cancer opens an entire new area for treating these cancers-- targeting pancreatic and biliary cancers using drugs, such as cyclopamine, that specifically inhibit the sonic hedgehog pathway. The team now plans to test a large panel of blockers ("inhibitors") of the sonic hedgehog pathway to determine which inhibitor provides the maximum anti-tumor effect and the minimum side effects. Third, the study is an example of what, in my opinion, makes Hopkins such a special place- the willingness of creative scientists from very diverse fields to work together to tackle big problems. Fourth, the creation of the cell lines and cancer xenografts that were central to this research was made possible by private donations. This is a wonderful example of how private philanthropy can support cutting edge research and have a significant impact in the war on cancer.

Johns Hopkins Is Number One AgainJuly 2003

THE JOHNS HOPKINS HOSPITAL TOPS U.S.NEWS & WORLD REPORT'S "HONOR ROLL" FOR THE 13th YEAR IN A ROW

For the 13th consecutive year, Johns Hopkins comes in at the very top of the list in the U.S. News & World Report's annual ranking of American hospitals. Hopkins ranked in the top 10 in 16 of 17 specialties, including cancer. Ratings are based on reputation (ranking by randomly selected physicians), mortality rates, and hospital factors such as discharges, ratio of nurses to beds, technology services, hospice/palliative care services, and whether or not the hospital is an NCI Cancer Center.

New Targets for Aberrant Methylation in Pancreas CancerJuly 10, 2003

Research by Norihiro Sato MD, PhD in the laboratory of Dr. Michael Goggins has led to the discovery of multiple genes that undergo silencing by methylation in pancreatic cancer. Knowledge of these genes provides us with a better understanding of the role of DNA methylation in pancreatic cancer development. The authors also showed that these abnormally methylated genes can be detected in pancreatic juice from patients with pancreatic cancer and raising hopes that their detection could aid in the early diagnosis of pancreatic cancer.

Anti-Cancer Drug Can Lead to Cancer InvasionJuly 10, 2003

In the February 19th issue of the Journal of the National Cancer Institute, Sato and colleagues report an unexpected adverse effect of an anti-cancer drug that is used to remove "methyl" groups (carbon-hydrogen) from DNA. The authors find that this drug can switch on certain genes (matrix metalloproteinases) that lead to cancer invasion. This effect is the result of the removal of methyl groups that function to keep these genes switched off in pancreas cells.

Research by Johns Hopkins Kimmel Cancer Center specialists has uncovered a novel pathway in the origin of pancreatic cancers. The Notch pathway, normally turned off in adults, can be turned on after injury to the pancreas. See the Hopkins news release for more details.

Washington D.C. PanCAN Visits Johns HopkinsJune 22, 2003

On Saturday June 7, 2003 close to 25 members of the Washington D.C. PanCAN group visited Johns Hopkins. The visit was organized by Mary Zapor from PanCAN and Sandy Markowitz from Hopkins. The visitors toured some of the labs, spoke with the scientists, and listened to talks on the clinical treatment of pancreatic cancer from Drs. Yeo and Laheru. In the end, the group had an informal lunch with the doctors and scientists. The morning was educational, but most importantly it motivated the Hopkins docs to work that much harder in the battle against pancreatic cancer, and it gave the PanCAN visitors a sense of the breadth and depth of research going on at Hopkins and a sense of excitement that exists now in the research labs at Hopkins.

The visit demonstrates the value of patient advocates, physicians and scientists working together.

If you would like to learn more about how you can support pancreatic cancer research at Johns Hopkins visit our Support Page.

Animation Explaining Mouse Models of Pancreatic Cancer June 5, 2003

A number of you have asked us to explain the important, but very complex, work that Gloria Su, PhD does in her lab developing mouse models of pancreatic cancer. One of the Art as Applied to Medicine students here at Johns Hopkins, Christian Rose, has developed a web animation to explain Dr. Su's research. We have posted it on the research presentation page of this web site. It is a big file, so you will have to be patient downloading it. If you still have problems, try downloading the new Macromedia Flash Player 6. We hope you find this animation interesting and educational.

Fanconi Gene Abnormalities in Pancreatic CancerMay 8, 2003

Eight years ago while studying pancreatic cancers, the Kern Laboratory found mutations of a new gene. Soon, this laboratory and others working in other tumor systems found that mutations of the gene were often inherited, raising the risk for pancreatic, ovarian, and breast cancer when an individual inherits one bad copy of the gene. This was the second gene found to cause inherited breast cancer, thus leading to the gene name, BRCA2.

In a paper published in the May 15, 2003 issue of the journal Cancer Research, Dr. Michiel van der Heijden and colleagues, also working in the Kern Laboratory, is following up on that earlier discovery. They knew that BRCA2 was one of the genes that gives rise to a rare syndrome, Fanconi anemia, when two bad copies are inherited by an individual. Fanconi anemia causes skeletal abnormalities and progressive bone marrow failure, and genes other than BRCA2 are responsible for most cases of the syndrome. In each case, one needed to inherit two bad copies in order to develop the syndrome. But what if an individual only inherited one bad copy, a condition that was previously thought to be lacking any association with disease? Was it possible that some of these other Fanconi genes might play a role in pancreatic cancer? Dr. van der Heijden found the answer to be "Yes!"

The scientists studied two of the Fanconi genes, FANCC and FANCG. Inherited and new mutations were found in a number of pancreatic cancers. Some of these mutations are inherited, meaning that individuals were inheriting a risk for pancreatic cancer. Fanconi anemia gene mutations are found in about 1 in 300 persons in the general population, and in 1 in about 75 Ashkenazi Jews. It remains to be determined how much the risk of cancer increases for such persons, and whether cancers other than pancreatic cancer would be included in the higher risk. Dr. van der Heijden and colleagues had another interesting finding; three of the nine persons whose pancreas cancer had young onset (less than 50 years of age) had such mutations. He perhaps had discovered a fairly common cause of young-onset pancreatic cancer.

There are no easy tests for the kinds of Fanconi gene mutations now being studied, but such tests may become available in the future. Such testing is likely to be of clinical importance. Cells that are defective in the Fanconi genes are known from other research to be highly sensitive to certain chemicals. If may be possible in the future to recommend a different therapeutic regimen for patients with these mutations. More research in this exciting new area is needed.

Activin Abnormalities in Pancreatic CancerFebruary 15, 2003

Two years ago while studying pancreatic cancers in the Kern Laboratory, Dr. Gloria Su and colleagues identified mutations in a gene that allows cells to respond to the presence of the extracellular protein, activin. Activin is part of a major system that vertebrate cells use to control populations of cells during development. It now appeared that the adult tissues also used activin for a similar purpose. The cancer cells had lost this form of control by activin by evolving dysfunctional mutations in the type IB receptor for activin that would normally be present on the surface of cells.

In a paper to be published in the March 1, 2003 issue of the journal Cancer Research, Dr. Paula Hempen and colleagues, also working in the Kern Laboratory, have followed up on that earlier discovery. They find additional mutations of another form of the activin receptor, extending the numbers of tumors known to have abnormalities in the activin system. The newly discovered mutations are in the ACVR2 gene, the activin type 2 receptor. The ACVR2 gene mutations were found in nearly all gastrointestinal tumors that had defects in a DNA-repair pathway involved in familial forms of cancer, including families at high risk of colorectal, pancreatic, and endometrial cancers.

These activin receptor mutations seem to be a fundamental change, without which the tumors perhaps could not occur. Dr. Byungwoo Ryu and colleagues in the Kern Laboratory therefore studied the genes that respond to activin signals to uncover the ways in which the cells are regulated by activin. Using a high-density gene expression screen, they studied gene expression changes characteristic of activin. Some of the genes regulated include genes that directly control cell division. This work is currently in press at the journal Cancer Biology & Therapy, and represents the largest study of gene responses to activin published to date.

New Animation Details Anti-PC VaccineJanuary 27, 2003

We've added an animation to our Website to describe the pancreas cancer vaccine being developed by Dr. Liz Jaffee here at Johns Hopkins. Created by a Medical Arts student, Helen MacFarlane, the animation helps the layperson understand how the vaccine is made and how it works. The vaccine is currently in a Phase 2 trial and is still enrolling participants. Click here to view the animation and learn more about this vaccine.